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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Anti-Cocaine Vaccine Based on Coupling a Cocaine Analog to a Disrupted Adenovirus

Author(s): George Koob, Martin J. Hicks, Sunmee Wee, Jonathan B. Rosenberg, Bishnu P. De, Stephen M. Kaminksy, Amira Moreno, Kim D. Janda and Ronald G. Crystal

Volume 10, Issue 8, 2011

Page: [899 - 904] Pages: 6

DOI: 10.2174/187152711799219334

Price: $65

Abstract

The challenge in developing an anti-cocaine vaccine is that cocaine is a small molecule, invisible to the immune system. Leveraging the knowledge that adenovirus (Ad) capsid proteins are highly immunogenic in humans, we hypothesized that linking a cocaine hapten to Ad capsid proteins would elicit high-affinity, high-titer antibodies against cocaine, sufficient to sequester systemically administered cocaine and prevent access to the brain, thus suppressing cocaine-induced behaviors. Based on these concepts, we developed dAd5GNE, a disrupted E1-E3- serotype 5 Ad with GNE, a stable cocaine analog, covalently linked to the Ad capsid proteins. In pre-clinical studies, dAd5GNE evoked persistent, high titer, high affinity IgG anti-cocaine antibodies, and was highly effective in blocking cocaine-induced hyperactivity and cocaine self-administration behavior in rats. Future studies will be designed to expand the efficacy studies, carry out relevant toxicology studies, and test dAd5GNE in human cocaine addicts.

Keywords: dAd5GNE, Cocaine, Addiction, Adenovirus, Vaccine, Anti-coccaine antibody, passive immunity, keyhole limpet hemocyanin, EDC, E1-E3-, Sensory nerve action potential, Palmitoylethanolamide, Laser evoked potential


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